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Genomic biomarkers related to drug response in Venezuelan populations

  • Miguel Angel Chiurillo EMAIL logo
Published/Copyright: September 24, 2014
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Drug Metabolism and Personalized Therapy
From the journal Drug Metabolism and Personalized Therapy Volume 30 Issue 1

Abstract

Pharmacogenetics is being applied to develop individual specific therapies considering different ethnic groups and mixed populations. The Venezuelan population is very heterogeneous as a result of the admixture process that occurred between Native Americans, Europeans, and Africans through five centuries. This review provides a summary of the literature concerning gene variants within drug-metabolizing enzymes, drug targets, and drug receptors (CYP2C19, CYP2D6, GSTM1, GSTT1, GSTP1, NAT2, MTHFR, LEP, LEPR, LTC4S, and ADRβ2 genes) evaluated in the Venezuelan population. In particular, most of the studies were conducted with relatively low numbers of individuals. Some of these studies included analyses of genetic polymorphisms in native groups living in this country. Although the recent studies represent a hopeful progress toward the inclusion of the Venezuelan population among those who will benefit from the implementation of pharmacogenetic principles and tools in drug therapy, there are not yet sufficient data concerning allelic frequencies of genomic biomarkers related to drug response for their implementation in clinical practice. Therefore, there is a critical need for more research in pharmacogenetics in Venezuela to increase data availability.

Keywords: cytochrome P450; drug-metabolizing enzymes; gene polymorphism; pharmacogenetics; receptors; single-nucleotide polymorphism (SNP); transporters; Venezuela
Corresponding author: Miguel Angel Chiurillo, Laboratorio de Genética Molecular “Dr. Yunis-Turbay”, Decanato de Ciencias de la Salud, Universidad Centroccidental Lisandro Alvarado, Barquisimeto 3001, Estado Lara, Venezuela, E-mail:

Acknowledgments

The studies conducted by the author were supported by the Universidad Centroccidental Lisandro Alvarado through grant CDCHT-UCLA 003-CS-2011. I would like to thank Miss N. Lander for revising the English in the manuscript.

Author contributions: The author has accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Ma Q, Lu AY. Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev 2011;63:437–59.10.1124/pr.110.003533Search in Google Scholar PubMed

2. Linder MW, Valdes R Jr. Genetic mechanisms for variability in drug response and toxicity. J Anal Toxicol 2001;25:405–13.10.1093/jat/25.5.405Search in Google Scholar PubMed

3. Ingelman-Sundberg M, Zhong XB, Hankinson O, Beedanagari S, Yu AM, Peng L, et al. Potential role of epigenetic mechanisms in the regulation of drug metabolism and transport. Drug Metab Dispos 2013;41:1725–31.10.1124/dmd.113.053157Search in Google Scholar PubMed PubMed Central

4. Kidd JM, Cooper GM, Donahue WF, Hayden HS, Sampas N, Graves T, et al. Mapping and sequencing of structural variation from eight human genomes. Nature 2008;453:56–64.10.1038/nature06862Search in Google Scholar PubMed PubMed Central

5. Consortium TGP. A map of human genome variation from population-scale sequencing. Nature 2010;467:1061–73.10.1038/nature09534Search in Google Scholar PubMed PubMed Central

6. Alwi ZB. The use of SNPs in pharmacogenomics studies. Malays J Med Sci 2005;12:4–12.Search in Google Scholar

7. Lee JE, Choi JH, Lee JH, Lee MG. Gene SNPs and mutations in clinical genetic testing: haplotype-based testing and analysis. Mutat Res 2005;573:195–204.10.1016/j.mrfmmm.2004.08.018Search in Google Scholar PubMed

8. Chen Q, Zhang T, Wang JF, Wei DQ. Advances in human cytochrome p450 and personalized medicine. Curr Drug Metab 2011;12:436–44.10.2174/138920011795495259Search in Google Scholar PubMed

9. Meyer UA. Cytochrome P450 enzymes. Drug Metabol Drug Interact 2012;27:1–2.10.1515/dmdi-2012-0002Search in Google Scholar PubMed

10. Ginsberg G, Smolenski S, Neafsey P, Hattis D, Walker K, Guyton KZ, et al. The influence of genetic polymorphisms on population variability in six xenobiotic-metabolzing enzymes. J Toxicol Environ Health B Crit Rev 2009;12:307–33.10.1080/10937400903158318Search in Google Scholar PubMed

11. Ortega VE, Meyers DA. Pharmacogenetics: implications of race and ethnicity on defining genetic profiles for personalized medicine. J Allergy Clin Immunol 2014;133:16–26.10.1016/j.jaci.2013.10.040Search in Google Scholar PubMed PubMed Central

12. Rodríguez-Larralde A, Castro de Guerra D, Gonzalez M, Morales J. Frecuencia génica y porcentaje de mezcla en diferentes áreas geográficas de Venezuela, de acuerdo a los grupos Rh y ABO. Interciencia 2001;26:8–12.Search in Google Scholar

13. Martínez H, Rodríguez-Larralde A, Izaguirre MH, Castro de Guerra D. Admixture estimates for Caracas, Venezuela, based on autosomal, Y-chromosome and mtDNA markers. Hum Biol 2007;79:201–13.10.1353/hub.2007.0032Search in Google Scholar PubMed

14. Guerra DC, Pérez CF, Izaguirre MH, Barahona EA, Larralde AR, Lugo MV. Gender differences in ancestral contribution and admixture in Venezuelan populations. Hum Biol 2011;83: 345–61.10.3378/027.083.0302Search in Google Scholar PubMed

15. Suarez-Kurtz G. Pharmacogenomics in admixed populations. Trends Pharmacol Sci 2005;26:196–201.10.1016/j.tips.2005.02.008Search in Google Scholar PubMed

16. Suarez-Kurtz G, Pena SD. Pharmacogenomics in the Americas: the impact of genetic admixture. Curr Drug Targets 2006;7:1649–58.10.2174/138945006779025392Search in Google Scholar PubMed

17. Bonilla C, Gutiérrez G, Parra EJ, Kline C, Shriver MD. Admixture analysis of a rural population of the state of Guerrero, Mexico. Am J Phys Anthropol 2005;128:861–9.10.1002/ajpa.20227Search in Google Scholar PubMed

18. Castro de Guerra D, Flores S, Izaguirre MH. Distribution of CYP2C19*2 and CYP2C19*3 polymorphisms in Venezuelan populations with different admixture. Ann Hum Biol 2013;40:197–200.10.3109/03014460.2012.749946Search in Google Scholar PubMed

19. Griman P, Moran Y, Valero G, Loreto M, Borjas L, Chiurillo MA. CYP2D6 gene variants in urban/admixed and Amerindian populations of Venezuela: pharmacogenetics and anthropological implications. Ann Hum Biol 2012;39:137–42.10.3109/03014460.2012.656703Search in Google Scholar PubMed

20. Chiurillo MA, Griman P, Santiago L, Torres K, Moran Y, Borjas L. Distribution of GSTM1, GSTT1, GSTP1 and TP53 disease-associated gene variants in native and urban Venezuelan populations. Gene 2013;531:106–11.10.1016/j.gene.2013.08.055Search in Google Scholar PubMed

21. Verhagen LM, Coenen MJ, López D, García JF, de Waard JH, Schijvenaars MM, et al. Full-gene sequencing analysis of NAT2 and its relationship with isoniazid pharmacokinetics in Venezuelan children with tuberculosis. Pharmacogenomics 2014;15:285–96.10.2217/pgs.13.230Search in Google Scholar PubMed

22. Selinski S, Blaszkewicz M, Agundez JA, Martinez C, Garcia-Martin E, Hengstler JG, et al. Clarifying haplotype ambiguity of NAT2 in multi-national cohorts. Front Biosci (Schol Ed) 2013;5:672–84.10.2741/S399Search in Google Scholar

23. Larocca N, Moreno D, Garmendia JV, Velasquez O, Martin-Rojo J, Talamo C, et al. Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator responses in adult Venezuelan asthmatic patients Beta 2 adrenergic receptor polymorphisms, at codons 16 and 27, and bronchodilator responses in adult Venezuelan asthmatic patients. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2013;157:374–8.10.5507/bp.2012.084Search in Google Scholar PubMed

24. Fernández E, Carrizo E, Fernández V, Connell L, Sandia I, Prieto D, et al. Polymorphisms of the LEP- and LEPR genes, metabolic profile after prolonged clozapine administration and response to the antidiabetic metformin. Schizophr Res 2010;121:213–7.10.1016/j.schres.2010.06.001Search in Google Scholar PubMed

25. Sánchez-Borges M, Acevedo N, Vergara C, Jiménez S, Zabner-Oziel P, Monzón A, et al. The A–444C polymorphism in the leukotriene C4 synthase gene is associated with aspirin-induced urticaria. J Investig Allergol Clin Immunol 2009;19:375–82.Search in Google Scholar

26. Chacín M, Ferraz S, Rivas A, Suárez G, Bravo-Urquiola M, Montilla S, et al. [C677T and A1298C MTHFR polymorphisms in Venezuelan population of different ethnicity] [abstract]. J Basic Appl Genet 2012;23(Suppl):114.Search in Google Scholar

27. Scott SA, Sangkuhl K, Gardner EE, Stein CM, Hulot JS, Johnson JA, et al. Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450-2C19 (CYP2C19) genotype and clopidogrel therapy. Clin Pharmacol Ther 2011;90:328–32.10.1038/clpt.2011.132Search in Google Scholar PubMed PubMed Central

28. Crews KR, Gaedigk A, Dunnenberger HM, Klein TE, Shen DD, Callaghan JT, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype. Clin Pharmacol Ther 2012;91:321–6.10.1038/clpt.2011.287Search in Google Scholar PubMed PubMed Central

29. The Human Cytochrome P450 (CYP) Allele Nomenclature Database. Available at: www.cypalleles.ki.se. Accessed on April 15, 2014.Search in Google Scholar

30. Linden R, Ziulkosk AL, Tonello P, Wingert M, Souto AA. Relation between CYP2C19 phenotype and genotype in a group of Brazilian volunteers. Braz J Pharm Sci 2009;45:461–7.10.1590/S1984-82502009000300011Search in Google Scholar

31. Chua EW, Kennedy MA. Current state and future prospects of direct-to-consumer pharmacogenetics. Front Pharmacol 2012;3:152.Search in Google Scholar

32. Zhou SF. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part I. Clin Pharmacokinet 48:689–723.10.2165/11318030-000000000-00000Search in Google Scholar PubMed

33. Isaza CA, Henao J, López AM, Cacabelos R. Isolation, sequence and genotyping of the drug metabolizer CYP2D6 gene in the Colombian population. Methods Find Exp Clin Pharmacol 2000;22:695–705.10.1358/mf.2000.22.9.802286Search in Google Scholar PubMed

34. Lopez M, Guerrero J, Jung-Cook H, Alonso ME. CYP2D6 genotype and phenotype determination in a Mexican Mestizo population. Eur J Clin Pharmacol 2005;61:749–54.10.1007/s00228-005-0038-2Search in Google Scholar PubMed

35. Shimizu T, Ochiai H, Asell F, Yokono Y, Kikuchi Y, Nitta M, et al. Bioinformatics research on interracial difference in drug metabolism I. Analysis on frequencies of mutant alleles and poor metabolizers on CYP2D6 and CYP2C19. Drug Metab Pharmacokinet 2003;18:71–8.10.2133/dmpk.18.71Search in Google Scholar PubMed

36. Mannervik B, Awasthi YC, Board PG, Hayes JD, Di Ilio C, Ketterer B, et al. Nomenclature for human glutathione transferases. Biochem J 1992;282:305–6.10.1042/bj2820305Search in Google Scholar PubMed PubMed Central

37. Frova C. Glutathione transferases in the genomics era: new insights and perspectives. Biomol Eng 2006;23:149–69.10.1016/j.bioeng.2006.05.020Search in Google Scholar PubMed

38. Parkin DP, Vandenplas S, Botha FJ, Vandenplas ML, Seifart HI, van Helden PD, et al. Trimodality of isoniazid elimination: phenotype and genotype in patients with tuberculosis. Am J Respir Crit Care Med 1997;155:1717–22.10.1164/ajrccm.155.5.9154882Search in Google Scholar PubMed

39. Torres MM, Acosta CP, Sicard DM, Groot de Restrepo H. [Genetic susceptibility and risk of gastric cancer in a human population of Cauca, Colombia]. Biomedica 2004;24:153–62.10.7705/biomedica.v24i2.1261Search in Google Scholar

40. Pérez-Morales R, Castro-Hernández C, Gonsebatt ME, Rubio J. Polymorphism of CYP1A1*2C, GSTM1*0, and GSTT1*0 in a Mexican Mestizo population: a similitude analysis. Hum Biol 2008;80:457–65.10.3378/1534-6617-80.4.457Search in Google Scholar PubMed

41. Garte S, Gaspari L, Alexandrie AK, Ambrosone C, Autrup H, Autrup JL, et al. Metabolic gene polymorphism frequencies in control populations. Cancer Epidemiol Biomarkers Prev 2001;10:1239–48.Search in Google Scholar

42. Geisler SA, Olshan AF. GSTM1, GSTT1, and the risk of squamous cell carcinoma of the head and neck: a mini-HuGE review. Am J Epidemiol 2001;154:95–105.10.1093/aje/154.2.95Search in Google Scholar PubMed

43. Zhang ZJ, Hao K, Shi R, Zhao G, Jiang GX, Song Y, et al. Glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms, smoking, and their interaction in oral cancer: a HuGE review and meta-analysis. Am J Epidemiol 2011;173:847–57.10.1093/aje/kwq480Search in Google Scholar PubMed

44. Ben Salah G, Kallabi F, Maatoug S, Mkaouar-Rebai E, Fourati A, Fakhfakh F, et al. Polymorphisms of glutathione S-transferases M1, T1, P1 and A1 genes in the Tunisian population: an intra and interethnic comparative approach. Gene 2012;498:317–22.10.1016/j.gene.2012.01.054Search in Google Scholar PubMed

45. Muñoz S, Vollrath V, Vallejos MP, Miquel JF, Covarrubias C, Raddatz A, et al. Genetic polymorphisms of CYP2D6, CYP1A1 and CYP2E1 in the South-Amerindian population of Chile. Pharmacogenetics1998;8:343–51.10.1097/00008571-199808000-00008Search in Google Scholar PubMed

46. Sosa-Macías M, Elizondo G, Flores-Pérez C, Flores-Pérez J, Bradley-Alvarez F, Alanis-Bañuelos RE, et al. CYP2D6 genotype and phenotype in Amerindians of Tepehuano origin and Mestizos of Durango, Mexico. J ClinPharmacol 2006;46:527–36.Search in Google Scholar

47. Bailliet G, Santos MR, Alfaro EL, Dipierri JE, Demarchi DA, Carnese FR, et al. Allele and genotype frequencies of metabolic genes in Native Americans from Argentina and Paraguay. Mutat Res 2007;627:171–7.10.1016/j.mrgentox.2006.11.005Search in Google Scholar PubMed

48. Gaspar PA, Hutz MH, Salzano FM, Hill K, Hurtado AM, Petzl-Erler ML, et al. Polymorphisms of CYP1A1, CYP2E1, GSTM1, GSTT1, and TP53 genes in Amerindians. Am J Phys Anthropol 2002;119:249–56.10.1002/ajpa.10128Search in Google Scholar PubMed

49. Ruiz Y, Chiurillo MA, Borjas L, Phillips C, Lareu MV, Carracedo Á, 2012. Analysis of the SNPforID 52-plex markers in four Native American populations from Venezuela. Forensic Sci Int Genet 2012;6:e142–5.10.1016/j.fsigen.2012.02.007Search in Google Scholar PubMed

50. Zabala-Fernández WM, Borjas-Fajardo L, Fernández Salgado E, Castillo C, Socca L, Portillo MG, et al. Use of short tandem repeats loci to study the genetic structure of several populations from Zulia State, Venezuela. Am J Hum Biol 2005;17:451–9.10.1002/ajhb.20409Search in Google Scholar PubMed

51. Lee AK, Bishop JR. Pharmacogenetics of leptin in antipsychotic-associated weight gain and obesity-related complications. Pharmacogenomics 2011;12:999–1016.10.2217/pgs.11.45Search in Google Scholar PubMed PubMed Central

52. Gregoor JG, van der Weide J, Loovers HM, van Megen HJ, Egberts TC, Heerdink ER. Polymorphisms of the LEP, LEPR and HTR2C gene: obesity and BMI change in patients using antipsychotic medication in a naturalistic setting. Pharmacogenomics 2011;12:919–23.10.2217/pgs.11.40Search in Google Scholar PubMed

53. Brandl EJ, Frydrychowicz C, Tiwari AK, Lett TA, Kitzrow W, Büttner S, et al. Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain. Prog Neuropsychopharmacol Biol Psychiatry 2012;38:134–41.10.1016/j.pnpbp.2012.03.001Search in Google Scholar PubMed

54. Kim SH, Sanak M, Park HS. Genetics of hypersensitivity to aspirin and nonsteroidal anti-inflammatory drugs. Immunol Allergy Clin North Am 2013;33:177–94.10.1016/j.iac.2012.10.003Search in Google Scholar PubMed

55. Cowburn AS, Sladek K, Soja J, Adamek L, Nizankowska E, Szczeklik A, et al. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. J Clin Invest 1998;101:834–46.10.1172/JCI620Search in Google Scholar PubMed PubMed Central

56. Celik G, Bavbek S, Misirligil Z, Melli M. Release of cysteinyl leukotrienes with aspirin stimulation and the effect of prostaglandin E(2) on this release from peripheral blood leucocytes in aspirin-induced asthmatic patients. Clin Exp Allergy 2001;31:1615–22.10.1046/j.1365-2222.2001.01074.xSearch in Google Scholar PubMed

57. Toffoli G, De Mattia E. Pharmacogenetic relevance of MTHFR polymorphisms. Pharmacogenomics 2008;9:1195–206.10.2217/14622416.9.9.1195Search in Google Scholar PubMed

58. De Mattia E, Toffoli G. C677T and A1298C MTHFR polymorphisms, a challenge for antifolate and fluoropyrimidine-based therapy personalisation. Eur J Cancer 2009;45:1333–51.10.1016/j.ejca.2008.12.004Search in Google Scholar PubMed

59. Quinones LA, Lavanderos MA, Cayun JP, Garcia-Martin E, Agundez JA, Caceres DD, et al. Perception of the usefulness of drug/gene pairs and barriers for pharmacogenomics in Latin America. Curr Drug Metab 2014;15:202–8.10.2174/1389200215666140202220753Search in Google Scholar PubMed

Received: 2014-5-16
Accepted: 2014-8-17
Published Online: 2014-9-24
Published in Print: 2015-3-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. From DMDI “Drug Metabolism and Drug Interactions” to DMPT “Drug Metabolism and Personalized Therapy”
  4. Review
  5. Clinical drug-drug interactions: focus on venlafaxine
  6. Reviews in Population Pharmacogenomics
  7. Pharmacogenetics in Central American healthy volunteers: interethnic variability
  8. Genomic biomarkers related to drug response in Venezuelan populations
  9. Originial Articles
  10. No effect of CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) on lipid-lowering response to statins in Greek patients with primary hypercholesterolemia
  11. Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans
  12. Effect of rifampin on the pharmacokinetics of bosutinib, a dual Src/Abl tyrosine kinase inhibitor, when administered concomitantly to healthy subjects
  13. Minor contribution of biliary excretion in lithium elimination in rats
  14. Case Report
  15. Fatal hyperkalemia following succinylcholine administration in a child on oral propranolol
https://doi.org/10.1515/dmdi-2014-0019
Keywords for this article
cytochrome P450; drug-metabolizing enzymes; gene polymorphism; pharmacogenetics; receptors; single-nucleotide polymorphism (SNP); transporters; Venezuela

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. From DMDI “Drug Metabolism and Drug Interactions” to DMPT “Drug Metabolism and Personalized Therapy”
  4. Review
  5. Clinical drug-drug interactions: focus on venlafaxine
  6. Reviews in Population Pharmacogenomics
  7. Pharmacogenetics in Central American healthy volunteers: interethnic variability
  8. Genomic biomarkers related to drug response in Venezuelan populations
  9. Originial Articles
  10. No effect of CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) on lipid-lowering response to statins in Greek patients with primary hypercholesterolemia
  11. Chloral hydrate, through biotransformation to dichloroacetate, inhibits maleylacetoacetate isomerase and tyrosine catabolism in humans
  12. Effect of rifampin on the pharmacokinetics of bosutinib, a dual Src/Abl tyrosine kinase inhibitor, when administered concomitantly to healthy subjects
  13. Minor contribution of biliary excretion in lithium elimination in rats
  14. Case Report
  15. Fatal hyperkalemia following succinylcholine administration in a child on oral propranolol
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